基于肿瘤发生机理的抗肿瘤药物
王晓东
由突变引起的肿瘤细胞生长失控和细胞凋亡导致肿瘤产生。目前对肿瘤的治疗主要是手术去除，合并放疗和化疗非特异性杀伤残存肿瘤细胞，这种方法的缺点是由于同时杀伤正常生长细胞而产生的副作用和长期治疗引发的治疗拮抗作用。
解决这一问题的途径就是要清楚了解肿瘤细胞的生长控制和凋亡途径特征性变化，如肿瘤的发生、肿瘤的生存和肿瘤对治疗的拮抗，进而针对这些变化从化学和生物方面寻找治疗途径。
一个成功的实例如Gleevac可作用于某种白血病产生的融合蛋白Bcr-abl而达到治疗目的。此次会议我将介绍两种新的针对肿瘤细胞控制的方法。
一种是用自然海洋产品Diazonamide
A阻断细胞分裂中的一种蛋白，这种蛋白在肿瘤细胞分裂中的作用较之正常细胞更为活跃。另一种是Smac的相似物，这一化学合成物可特异作用在凋亡蛋白抑制物上，从而促使肿瘤细胞的凋亡，使正常细胞优势生长。
随着越来越多抑制细胞生长和诱导细胞凋亡，尤其针对肿瘤细胞的化学合成物和生物制品的出现，可以预见联合使用这些手段将使得治疗肿瘤更为有效，同时副作用更小。
Developing Mechanism Based
Anti-cancer Drugs
Cancer arises from mutations that render cancer cells uncontrolled
growthand defective in apoptosis. The current cancer therapies mainly rely
on surgical removal of tumor mass in combination with radiation and
chemotherapy that induce cancer cell death through non-specific damage.
The drawbacks are side effects caused by the death of normal growing cells and
development of resistance to these treatments.
One way to counter these problems is to identify the specific changes in
the growth control and apoptotic pathways in cancer cells that contribute to
tumorgenesis, tumor maintenance and resistance to therapy and design chemical
and biological strategies to target these changes. Successful examples
include Gleevac that targets Bcr-abl fusion protein that generates only in
certain leukemia. At this meeting, I am going to present two new ways to
target cancer cells specifically. One is to use a derivative of a marine natural
product Diazonamide A to block cell division targeting a novel cellular protein
whose role in cell division seems prominently used in a variety of cancer cells.
The other is to develop Smac mimetics,chemicals that target cancer cells using
Inhibitor of Apoptotic Protein (IAP) to gain survival advantage.
With more and more compounds and biological agents becoming available,
which inhibit cell growth and induce apoptosis specifically in cancer cells, one
can envision that the combinational use of these agents will become much more
efficacious with less side effects.
